Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis
Por:
Marquez, A, Ferreiro-Iglesias, A, Davila-Fajardo, CL, Montes, A, Pascual-Salcedo, D, Perez-Pampin, E, Moreno-Ramos, MJ, Garcia-Portales, R, Navarro, F, Moreira, V, Magro, C, Caliz, R, Ferrer, MA, Alegre-Sancho, JJ, Joven, B, Carreira, P, Balsa, A, Vasilopoulos, Y, Sarafidou, T, Cabeza-Barrera, J, Narvaez, J, Raya, E, Canete, JD, Fernandez-Nebro, A, Ordonez, MD, de la Serna, AR, Magallares, B, Gomez-Reino, JJ, Gonzalez, A, Martin, J
Publicada:
1 ene 2014
Resumen:
Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations.
Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients.
Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis.
Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.
Filiaciones:
Marquez, A:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Ferreiro-Iglesias, A:
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Lab Invest 10, E-15706 Santiago, Spain
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Rheumatol Unit, E-15706 Santiago, Spain
Davila-Fajardo, CL:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Hosp Univ San Cecilio, Inst Invest Biosanitaria Granada IBIG, Dept Clin Pharm, E-18012 Granada, Spain
Montes, A:
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Lab Invest 10, E-15706 Santiago, Spain
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Rheumatol Unit, E-15706 Santiago, Spain
Pascual-Salcedo, D:
Hosp La Paz, Hosp Univ La Paz IdiPAZ, Inst Invest Sanitaria, Dept Immunol,Res Network Inflammat & Rheumat Dis, E-28046 Madrid, Spain
Perez-Pampin, E:
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Lab Invest 10, E-15706 Santiago, Spain
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Rheumatol Unit, E-15706 Santiago, Spain
Moreno-Ramos, MJ:
Hosp Virgen Arrixaca, Dept Rheumatol, El Palmar Murcia 30120, Spain
Garcia-Portales, R:
Hosp Virgen Victoria, Dept Rheumatol, Malaga 29010, Spain
Navarro, F:
Hosp Univ Virgen Macarena, Rheumatol Unit, Seville 41007, Spain
Moreira, V:
Hosp Univ Virgen Macarena, Rheumatol Unit, Seville 41007, Spain
Magro, C:
Hosp Clin San Cecilio, Dept Rheumatol, E-18012 Granada, Spain
Caliz, R:
Hosp Univ Virgen Nieves, Rheumatol Unit, E-18014 Granada, Spain
Ferrer, MA:
Hosp Univ Virgen Nieves, Rheumatol Unit, E-18014 Granada, Spain
Alegre-Sancho, JJ:
Hosp Doctor Peset, Dept Rheumatol, Valencia 46017, Spain
Joven, B:
Hosp Univ 12 Octubre, Res Network Inflammat & Rheumat Dis RIER, Inst Invest I 12, Dept Rheumatol, E-28041 Madrid, Spain
Carreira, P:
Hosp Univ 12 Octubre, Res Network Inflammat & Rheumat Dis RIER, Inst Invest I 12, Dept Rheumatol, E-28041 Madrid, Spain
Balsa, A:
Hosp Univ La Paz IdiPAZ, Inst Invest Sanitaria, Dept Rheumatol, Res Network Inflammat & Rheumat Dis RIER, E-28046 Madrid, Spain
Vasilopoulos, Y:
Univ Thessaly, Dept Biochem & Biotechnol, Larisa 41221, Greece
Sarafidou, T:
Univ Thessaly, Dept Biochem & Biotechnol, Larisa 41221, Greece
Cabeza-Barrera, J:
Hosp Univ San Cecilio, Inst Invest Biosanitaria Granada IBIG, Dept Clin Pharm, E-18012 Granada, Spain
Narvaez, J:
Hosp Univ Bellvitge, Dept Rheumatol, Barcelona 08907, Spain
Raya, E:
Hosp Clin San Cecilio, Dept Rheumatol, E-18012 Granada, Spain
Canete, JD:
Hosp Clin Barcelona, Dept Rheumatol, E-08036 Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, E-08036 Barcelona, Spain
Fernandez-Nebro, A:
Hosp Reg Univ Malaga, Inst Invest Biomed Malaga IBIMA, Unidad Gestion Clin UGC Rheumatol, Malaga 29010, Spain
Ordonez, MD:
Hosp Reg Univ Malaga, Inst Invest Biomed Malaga IBIMA, Unidad Gestion Clin UGC Rheumatol, Malaga 29010, Spain
de la Serna, AR:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona 08026, Spain
Magallares, B:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona 08026, Spain
Gomez-Reino, JJ:
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Lab Invest 10, E-15706 Santiago, Spain
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Rheumatol Unit, E-15706 Santiago, Spain
Univ Santiago de Compostela, Dept Med, Santiago De Compostela 15782, Spain
Gonzalez, A:
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Lab Invest 10, E-15706 Santiago, Spain
Univ Santiago, Inst Invest Sanitaria Hosp Clin, Rheumatol Unit, E-15706 Santiago, Spain
Martin, J:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain
Gold, Green Published
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